Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food & Drug Administration, 1401 Rockville Pike, Rockville, MD, USA.
Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food & Drug Administration, 1401 Rockville Pike, Rockville, MD, USA.
Regul Toxicol Pharmacol. 2014 Apr;68(3):468-74. doi: 10.1016/j.yrtph.2014.02.005. Epub 2014 Feb 15.
In pharmacokinetics, vertical allometry is referred to the clearance of a drug when the predicted human clearance is substantially higher than the observed human clearance. Vertical allometry was initially reported for diazepam based on a 33-fold higher human predicted clearance than the observed human clearance. In recent years, it has been found that many other drugs besides diazepam, can be classified as drugs which exhibit vertical allometry. Over the years, many questions regarding vertical allometry have been raised. For example, (1) How to define and identify the vertical allometry? (2) How much difference should be between predicted and observed human clearance values before a drug could be declared 'a drug which follows vertical allometry'? (3) If somehow one can identify vertical allometry from animal data, how this information can be used for reasonably accurate prediction of clearance in humans? This report attempts to answer the aforementioned questions. The concept of vertical allometry at this time remains complex and obscure but with more extensive works one can have better understanding of 'vertical allometry'.
在药代动力学中，垂直变异性是指当预测的人体清除率明显高于观察到的人体清除率时药物的清除率。最初根据预测的人体清除率比观察到的人体清除率高 33 倍，报道了安定的垂直变异性。近年来，除了安定之外，还发现许多其他药物可以归类为表现出垂直变异性的药物。多年来，人们提出了许多关于垂直变异性的问题。例如，（1）如何定义和识别垂直变异性？（2）在宣布一种药物“遵循垂直变异性”之前，预测的人体清除率与观察到的人体清除率值之间应该有多大差异？（3）如果可以从动物数据中识别出垂直变异性，如何利用这些信息对人体清除率进行合理准确的预测？本报告试图回答上述问题。目前，垂直变异性的概念仍然复杂而模糊，但随着更广泛的研究，可以更好地理解“垂直变异性”。
